Two new atom centered fragment descriptors and scoring function enhance classification of antibacterial activity

Classification of pharmacologic activity of a chemical compound is an essential step in any drug discovery process. We develop two new atom-centered fragment descriptors (vertex indices) - one based solely on topological considerations without discriminating atomor bond types, and another based on topological and electronic features. We also assess their usefulness by devising a method to rank and classify molecules with regard to their antibacterial activity. Classification performances of our method are found to be superior compared to two previous studies on large heterogeneous data sets for hit finding and hit-to-lead studies even though we use much fewer parameters. It is found that for hit finding studies topological features (simple graph) alone provide significant discriminating power, and for hit-to-lead process small but consistent improvement can be made by additionally including electronic features (colored graph). Our approach is simple, interpretable, and suitable for design of molecules as we do not use any physicochemical properties. The singular use of vertex index as descriptor, novel range based feature extraction, and rigorous statistical validation are the key elements of this study.

Multi Label Classification of Discrete Data

The paper describes an algorithm for multi-label classification. Since a pattern can belong to more than one class, the task of classifying a test pattern is a challenging one. We propose a new algorithm to carry out multi-label classification which works for discrete data. We have implemented the algorithm and presented the results for different multi-label data sets. The results have been compared with the algorithm multi-label KNN or ML-KNN and found to give good results.

Fuzzy Classification of Time Series Data

The problem of classification of time series data is an interesting problem in the field of data mining. Even though several algorithms have been proposed for the problem of time series classification we have developed an innovative algorithm which is computationally fast and accurate in several cases when compared with 1NN classifier. In our method we are calculating the fuzzy membership of each test pattern to be classified to each class. We have experimented with 6 benchmark datasets and compared our method with 1NN classifier.

A radial differential mobility analyzer for the size-classification of gas-phase synthesized nanoparticles at low pressures

Differential mobility analyzers (DMAs) are commonly used to generate monodisperse nanoparticle aerosols. Commercial DMAs operate at quasi-atmospheric pressures and are therefore not designed to be vacuum-tight. In certain particle synthesis methods, the use of a vacuum-compatible DMA is a requirement as a process step for producing high-purity metallic particles. A vacuum-tight radial DMA (RDMA) has been developed and tested at low pressures. Its performance has been evaluated by using a commercial NANO-DMA as the reference. The performance of this low-pressure RDMA (LP-RDMA) in terms of the width of its transfer function is found to be comparable with that of other NANO-DMAs at atmospheric pressure and is almost independent of the pressure down to 30 mbar. It is shown that LP-RDMA can be used for the classification of nanometer-sized particles (5-20 nm) under low pressure condition (30 mbar) and has been successfully applied to nanoparticles produced by ablating FeNi at low pressures.

Phylogenetic relationships and classification of thiolases and thiolase-like proteins of Mycobacterium tuberculosis and Mycobacterium smegmatis

Thiolases are enzymes involved in lipid metabolism. Thiolases remove the acetyl-CoA moiety from 3-ketoacyl-CoAs in the degradative reaction. They can also catalyze the reverse Claisen condensation reaction, which is the first step of biosynthetic processes such as the biosynthesis of sterols and ketone bodies. In human, six distinct thiolases have been identified. Each of these thiolases is different from the other with respect to sequence, oligomeric state, substrate specificity and subcellular localization. Four sequence fingerprints, identifying catalytic loops of thiolases, have been described. In this study genome searches of two mycobacterial species (Mycobacterium tuberculosis and Mycobacterium smegmatis), were carried out, using the six human thiolase sequences as queries. Eight and thirteen different thiolase sequences were identified in M. tuberculosis and M. smegmatis, respectively. In addition, thiolase-like proteins (one encoded in the Mtb and two in the Msm genome) were found. The purpose of this study is to classify these mostly uncharacterized thiolases and thiolase-like proteins. Several other sequences obtained by searches of genome databases of bacteria, mammals and the parasitic protist family of the Trypanosomatidae were included in the analysis. Thiolase-like proteins were also found in the trypanosomatid genomes, but not in those of mammals. In order to study the phylogenetic relationships at a high confidence level, additional thiolase sequences were included such that a total of 130 thiolases and thiolase-like protein sequences were used for the multiple sequence alignment. The resulting phylogenetic tree identifies 12 classes of sequences, each possessing a characteristic set of sequence fingerprints for the catalytic loops. From this analysis it is now possible to assign the mycobacterial thiolases to corresponding homologues in other kingdoms of life. The results of this bioinformatics analysis also show interesting differences between the distributions of M. tuberculosis and M. smegmatis thiolases over the 12 different classes. (C) 2014 Elsevier Ltd. All rights reserved.

CLAP: A web-server for automatic classification of proteins with special reference to multi-domain proteins

Background: The function of a protein can be deciphered with higher accuracy from its structure than from its amino acid sequence. Due to the huge gap in the available protein sequence and structural space, tools that can generate functionally homogeneous clusters using only the sequence information, hold great importance. For this, traditional alignment-based tools work well in most cases and clustering is performed on the basis of sequence similarity. But, in the case of multi-domain proteins, the alignment quality might be poor due to varied lengths of the proteins, domain shuffling or circular permutations. Multi-domain proteins are ubiquitous in nature, hence alignment-free tools, which overcome the shortcomings of alignment-based protein comparison methods, are required. Further, existing tools classify proteins using only domain-level information and hence miss out on the information encoded in the tethered regions or accessory domains. Our method, on the other hand, takes into account the full-length sequence of a protein, consolidating the complete sequence information to understand a given protein better. Results: Our web-server, CLAP (Classification of Proteins), is one such alignment-free software for automatic classification of protein sequences. It utilizes a pattern-matching algorithm that assigns local matching scores (LMS) to residues that are a part of the matched patterns between two sequences being compared. CLAP works on full-length sequences and does not require prior domain definitions. Pilot studies undertaken previously on protein kinases and immunoglobulins have shown that CLAP yields clusters, which have high functional and domain architectural similarity. Moreover, parsing at a statistically determined cut-off resulted in clusters that corroborated with the sub-family level classification of that particular domain family. Conclusions: CLAP is a useful protein-clustering tool, independent of domain assignment, domain order, sequence length and domain diversity. Our method can be used for any set of protein sequences, yielding functionally relevant clusters with high domain architectural homogeneity. The CLAP web server is freely available for academic use at http://nslab.mbu.iisc.ernet.in/clap/.

Framework for morphometric classification of cells in imaging flow cytometry

Imaging flow cytometry is an emerging technology that combines the statistical power of flow cytometry with spatial and quantitative morphology of digital microscopy. It allows high-throughput imaging of cells with good spatial resolution, while they are in flow. This paper proposes a general framework for the processing/classification of cells imaged using imaging flow cytometer. Each cell is localized by finding an accurate cell contour. Then, features reflecting cell size, circularity and complexity are extracted for the classification using SVM. Unlike the conventional iterative, semi-automatic segmentation algorithms such as active contour, we propose a noniterative, fully automatic graph-based cell localization. In order to evaluate the performance of the proposed framework, we have successfully classified unstained label-free leukaemia cell-lines MOLT, K562 and HL60 from video streams captured using custom fabricated cost-effective microfluidics-based imaging flow cytometer. The proposed system is a significant development in the direction of building a cost-effective cell analysis platform that would facilitate affordable mass screening camps looking cellular morphology for disease diagnosis. Lay description In this article, we propose a novel framework for processing the raw data generated using microfluidics based imaging flow cytometers. Microfluidics microscopy or microfluidics based imaging flow cytometry (mIFC) is a recent microscopy paradigm, that combines the statistical power of flow cytometry with spatial and quantitative morphology of digital microscopy, which allows us imaging cells while they are in flow. In comparison to the conventional slide-based imaging systems, mIFC is a nascent technology enabling high throughput imaging of cells and is yet to take the form of a clinical diagnostic tool. The proposed framework process the raw data generated by the mIFC systems. The framework incorporates several steps: beginning from pre-processing of the raw video frames to enhance the contents of the cell, localising the cell by a novel, fully automatic, non-iterative graph based algorithm, extraction of different quantitative morphological parameters and subsequent classification of cells. In order to evaluate the performance of the proposed framework, we have successfully classified unstained label-free leukaemia cell-lines MOLT, K562 and HL60 from video streams captured using cost-effective microfluidics based imaging flow cytometer. The cell lines of HL60, K562 and MOLT were obtained from ATCC (American Type Culture Collection) and are separately cultured in the lab. Thus, each culture contains cells from its own category alone and thereby provides the ground truth. Each cell is localised by finding a closed cell contour by defining a directed, weighted graph from the Canny edge images of the cell such that the closed contour lies along the shortest weighted path surrounding the centroid of the cell from a starting point on a good curve segment to an immediate endpoint. Once the cell is localised, morphological features reflecting size, shape and complexity of the cells are extracted and used to develop a support vector machine based classification system. We could classify the cell-lines with good accuracy and the results were quite consistent across different cross validation experiments. We hope that imaging flow cytometers equipped with the proposed framework for image processing would enable cost-effective, automated and reliable disease screening in over-loaded facilities, which cannot afford to hire skilled personnel in large numbers. Such platforms would potentially facilitate screening camps in low income group countries; thereby transforming the current health care paradigms by enabling rapid, automated diagnosis for diseases like cancer.